Analysis for the expression and localization of PKC isoform in colorectal cancer

蛋白激酶C(PKC)是一种信号转导中心的丝氨酸/苏氨酸激酶，与肿瘤的发生密切相关。目前，10PKC亚型已被克隆，但其确切的组织特异性作用尚未确定。为了确定在结直肠癌(CRC)中PKC是否降低，以及在人类结直肠癌进展过程中特定的PKC亚型是否发生改变，我们检测了特定的PKC亚型的mRNA和蛋白的表达。建立了17例结直肠癌、1例转移性肝肿瘤和2例原发性肝肿瘤的肿瘤库。PKC-α、Bll、Gamma、Delta、Eta(L)、epsilon和Zeta在所有组织中均有表达。PKC-α、Bll、Delta、ETa(L)、epsilon和Zeta在大多数原发癌中降低，PKC-β和Delta检测到PKC异构体蛋白定位的改变。癌组织中未检测到PKC-β。正常大肠粘膜中PKC-Delta表达于细胞膜下，癌组织呈弥漫性染色。由于大多数PKC亚型的mRNA在结直肠癌中的表达减少，先前报道的结直肠癌总的PKC活性的降低不仅仅是由于翻译后的酶修饰。由于某些PKC亚型在结直肠癌中的表达与正常结肠黏膜不同，我们的结果提示特定的PKC亚型可能与人类结直肠癌的进展有关。

Protein kinase C (PKC), a serine/threonine kinase central to signal transduction, is implicated in tumor promotion. At present, 10PKC isoforms have been cloned but their precise tissue-specific role has yet to be defined. In order to determine it PKC is reduced in colorectal cancers (CRC) and if specific PKC isoforms are altered in human CRC progression, specific PKC isoform mRNA and protein expression were examined. We established tumor bank that involved 17 cases of colorectal cancer, one case of metastatic liver tumor and two cases of primary liver tumor. PKC-alpha, Bll, gamma, delta, eta (L), epsilon and zeta were expressed in all tissues. PKC-alpha, Bll, delta, eta (L), epsilon and zeta were decreased in most primary CRC.Alteration of the localization of PKC isoform protein is examined in PKC-beta and delta. PKC-beta could not be detected in cancer tissue. PKC-delta was expressed under sub-cellularmembrane in normal colonic mucosa although cancer showed diffuse staining. Since mRNA expression for most PKC isoforms is decreased in CRC,the previously reported decreases in overall PKC activity in CRC are not solely due to a post-translational enzyme modification. Since certain PKC isoforms were expressed uniquely different in CRC relative to normal colonic mucosa, our resutls suggest that specific PKC isoforms may be involved in human CRC progression.